The research is intended to test reciprocating-subunit, or flip-flop, mechanisms that have been proposed to explain evidence for subunit interaction in two enzymes, horse-liver alcohol dehydrogenase and pig-heart mitochondrial malate dehydrogenase. However, the project has two broader goals: (1) development of a general strategy for testing hypothesized subunit reciprocation in any symmetrical dimeric enzyme; and (2) creation of a class of covalent protein modifying reagents that can be used whenever it is desirable to test the stoichiometry and randomness of modification.